Apply to change your trial’s protocol or documentation

These changes count as a substantial amendment to your clinical trial authorisation. You need to send a notification of amendment form, a revised application form and other documents to the Medicines and Healthcare Products Regulatory Agency (MHRA):

covering letter outlining the substantial and any non-substantial changes

proof of payment of your fee - see guidance on making a payment for more information on the types of documents that can be submitted to avoid issues with your application - you should state your EudraCT number, which is used as a reference number

reasons for the proposed changes

proposed changes to the protocol or other document (eg investigational medicinal product dossier), showing previous and new wording

General CESP training is available to all registered users via CESP’s training menu once logged into the system. Training on demand videos are available and you can also sign up to our free online weekly live demonstrations. CESP encourage all users to attend training before using the system.

Assessment process

We will assess your application within 35 days. Healthy volunteer trials and sponsor-determined phase I trials in non-oncology patients may qualify for a shorter assessment time (average 14 days). State in the heading of your covering letter if you think your trial is eligible.

Invalid applications

If your application does not meet the requirements it will not be assessed. You will be told the reasons why your application is invalid, which could include:

Change your contact details

The email must be sent as a signed and scanned attachment by the contact person listed on the application form and must include:

EudraCT number

CTA number

Protocol number

details of the previous contact person and/or contact details

details of the new contact person and/or contact details, to include:

The new contact person or details should be updated on the application form (which is part of your initial application form) and an updated XML should be included in the next submission of a substantial amendment so that the details can be uploaded into EudraCT.

Change of sponsor or legal representative

If you want to change the sponsor or legal representative for your study you must submit a substantial amendment to MHRA. You can’t include any other changes with this amendment.

You can’t submit any other substantial amendments until you have confirmation from MHRA that the sponsor or legal representative has been changed.

If your want to change your sponsor you must include these documents with your submission:

a cover letter that includes the date of transfer of responsibilities

a letter on headed company paper from the current sponsor confirming the transfer of the study

a letter on headed company paper from the new sponsor confirming that they accept the role of sponsor for this study

a signed notification of amendment (Annex 2) form (PDF)

an updated PDF and xml file of the clinical trial application form (Annex I) signed by the new sponsor or person acting on behalf of the sponsor

Other company documents don’t need to be submitted as part of this submission, eg protocol. There is no fee for a change of sponsor amendment

During the assessment of your amendment the old and new sponsor will receive an administrative letter confirming that the change has been registered. You don’t need to wait for MHRA confirmation before making the sponsor change.

Clinical trials named contact

Effective from 27th June 2016, persons other than the applicant named in the trial application form, who call or email the MHRA CTU helpline, reports to be from the sponsor/applicants company and knows the EudraCT number and security word/phrase (previously provided to MHRA by the named applicant) for a trial may obtain information on that trial.

For ongoing studies, the applicant named in section C.1 of the application form should notify the Clinical Trials Unit of their chosen security word/phrase by emailing clintrialhelpline@mhra.gsi.gov.uk with ‘Clinical Trials named contact’ as the subject line and listing the EudraCT number(s) in the body of the email.

For new applications, the applicant named in section C.1 of the application form is requested to include the security word/phrase in the cover letter for the submission.

Report an urgent safety issue

As a sponsor or trial investigator, you must act immediately if you find a safety issue during a clinical trial to protect subjects from any immediate threat to their health and safety.

Phone the MHRA’s Clinical Trial Unit on 020 3080 6456 to discuss the issue with a safety scientist, ideally within 24 hours. If we need more information a medical assessor will contact you.

You must then inform MHRA in writing within 3 days of the incident. MHRA will tell you how to do this when you speak to them, but it will usually be by email. Written notification in the form of a substantial amendment (annex 2) is also required.

What to report to MHRA

You must report all suspected unexpected serious adverse reactions (SUSARs) which happen during the course of the trial to MHRA.

You must report fatal or life-threatening SUSARs as soon as possible, but no later than 7 days after you are first aware of the reaction. Any additional relevant information must be sent within 8 days of the report.

You must report non-fatal or non-life-threatening SUSARs as soon as possible but no later than 15 days after you are first aware of the reaction.

You must report all UK-relevant SUSARs to MHRA.

The agency’s definition of ‘UK-relevant’ includes:

SUSARs originating in the UK

SUSARs originating outside the UK where the sponsor has an ongoing trial in the UK involving the same medicinal product

You must keep detailed records of all adverse reactions relating to a clinical trial. MHRA may require you to send copies of records if there is an investigation.

You will need to register your details with us before using the eSUSAR website. You should complete the eSUSAR registration form
(MS Word Document, 44.5KB)
and email it to esusar@mhra.gsi.gov.uk with the subject line ‘eSUSAR registration’.

At the end of the DSUR reporting period the sponsor may assess the new safety information that has been generated and submit any proposed safety changes to the investigator’s brochure as a substantial amendment. This amendment should be supported by the DSUR and approved before the reference safety information (RSI) is changed.

The RSI for any investigational medicinal product involved in a clinical trial must stay consistent during each reporting period.

Suspend or terminate a trial

MHRA has the authority to make amendments to an authorisation or in certain circumstances suspend or terminate a trial. You can apply to MHRA to suspend or terminate your own trial.

Suspend a trial temporarily

The notification should be made as a substantial amendment using the notification of amendment form, clearly explaining what has been stopped and the reasons for the suspension.

Substantial amendments relating to temporary suspension and urgent safety measures must be submitted using CESP.

To restart a trial that has been temporarily suspended, you should make the request as a substantial amendment using the notification of amendment form, providing evidence that it is safe to restart the trial.

End of trial study report

The sponsor is responsible for uploading the end of trial summary results to EudraCT as per the commission’s guidelines on posting and publication of result-related information.

You don’t need to submit this clinical trial summary report to the MHRA as well however you must send a short confirmatory email to CT.Submission@mhra.gsi.gov.uk once the result-related information has been uploaded to EudraCT, with ‘End of trial : result-related information: EudraCT XXXX-XXXXXX-XX’ as the subject line. You will not get an acknowledgment email or letter.